glp, gcp & gmp harmonization - veeva systems · we compare the regulations, explore ... • the...

Jay Smith

Sparta Systems

[email protected]

GLP, GCP & GMP Harmonization

New expectations for a new world

GLP, GCP, and GMP regulations are often managed

independently. There are commonalities across these

guidelines and organizations are evaluating how to

harmonize approaches to compliance. We compare the

regulations, explore how leading companies have

created transparency between these phases, and share

insights on mitigating risk in an outsourced

environment.

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Presentation Outline

GLP, GCP, and GMP

Good Laboratory Practices

“A quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.”

GLPs are regulations published in:

• Code of Federal Regulations (21 CFR part 58)

• The OECD Principles of Good Laboratory Practice

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GLP Highlights

GLP is Non-clinical, animal studies, drug discovery 3.5 years GLP studies building the protocolRegulations are very old and strict 21 CFR 58.1GLP Quality Assurance Unit QAU is any person or org. element other than the study director Study director owns the study but QAU is responsible for qualityActivities include: Master Schedule Audits System Process Project/Program QA Statement

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Good Clinical Practices

“GCP is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.

Compliance with this standard provides public assurance that the rights, safety, and well being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical data are credible.”

GCPs are regulations published in:

• E6 Guideline for Good Clinical Practice, Code of Federal Regulations

• ICH Harmonization Tripartite Guideline

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GCP Highlights

GCP is the practice of medicine

Monitor study

Keep the patient safe

Drug Development, clinical trials

Drug development phases 1 to 3 (~8.5 years)

Drug Marketing / Expansion phases

Program (multiple studies)

Focused on a single compound

Responsibility by Sponsor and Principal Investigator

Key terms:

ICH Guideline (International Conference on Harmonization)

CRF – Case Report Form

PI – Principal Investigator

CRA – Clinical Monitor

AE/SAE – Adverse Event/Serious Adverse Event7

Good Manufacturing Practices

“Good manufacturing practice is the part of quality assurance

which ensures that products are consistently produced and

controlled to the quality standard appropriate to their intended

use and as required by the Marketing Authorization or product

specification. GMP is concerned with both production and

quality control.”

GMPs are regulations published in:

• Code of Federal Regulations (21 CFR part 210, 211, 820, etc.)

• EU Guidelines to GMP Medicinal products for human and

veterinary use

GMP Highlights

GMP is the manufacture of the drug or device

Have a Quality System in place and follow procedures. Maintain control

of manufacturing processes.

Capture and review complaints, deviations, CAPA, root cause, audits,

change control and effectiveness check for anyone who has a hand in

the manufacture of the final product or any component

Roles and Training

Manufacturing Facility

Owned by the head of production, executed by plant quality manager

Key terms:

Quality Management System

Batch Release

Manufacturing Authorization

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Lab IssuesDeviations/NCRs &

Incidents

Audit

Management

Investigations

Risk Evaluation

Root Cause Analysis

Effectiveness Check

Complaint

Handling

CAPA

Change ControlBatch / IT / Process / Document

Material / Equipment

Supplier Quality

Management


GxP and the Development Process

Drug DiscoveryPreclinical

DevelopmentClinical Trials I,

II, IIIManufacturing, APIs, QC

Labs

GLP GCP GMP

Study Based Process Based

ICH Q10

Critical Processes

GLP, GCP, GMP Audits

Auditing Overview

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Audits evaluate processes, systems, product and materials, people, or other corporate operations. Audits can be run internally, by

partners, customers, regulatory agencies, or third parties.

Purpose

• Ensure operations and procedures are within stated SOPs

• Serve as evaluations for decisions

• Ensure regulatory compliance

Description

• Audits are run periodically

• Auditors examine the area of focus

• Auditors provide observations, findings, and recommendations

• Action plans are generated using recommendations

Audit Cycle

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Planning Execution Follow-up

Audit Cycle

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• Audit lifecycle:

• Scheduling• Preparation• Design Audit

Templates• Report approval• Report issuance• Response • Corrective action

(CAPA) tracking

• Auditors document results

• Provide actionable data for tracking and trending

• Prioritize resources across audit types based on role and department

• Ensure appropriate action is taken (CAPAs) and audits are completed and closed out

• Audit reports that can be delivered as needed

Preclinical GLP and Clinical GCP Auditing

Audit

Master Schedule Entry

Finding

Finding

Finding

CAPA

CAPA

CAPA

CAPA

Clinical Study

Audit

Audit

Audit

Finding

Finding

CAPA

CAPA

Finding

Clinical Study

Clinical Study

Program

Preclinical GLP Clinical GCP

A Point Solution or Holistic Audit Management Solution?

Many companies utilize systems as point solutions for

audit management

Preclinical GLP Auditing

Clinical GCP Auditing

GMP Auditing

Auditing Across the Enterprise

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GLP GCP GMP Preclinical Studies Pharmacovigilance Audits Functional Audits Business Conduct Standards Compliance Validation Audits Contractor Compliance

Assessment

Internal Quality Audits Risk Assessments Internal Controls Contractor/Supplier/ Vendor Third Party (FDA, ISO &

other health) Process Audits Internal Facility Projects Method Validation Audits EH&S Audits

Bringing it All Together

What happens when you gather various auditing groups to build a common platform?

Example Audit Process

Triggered

Individually

Determine Audit Schedule

Schedule Audit Audit Preparation

Chose Template Estimate Dates Identify Site Identify Team

Audit Execution

On-line Off-line

Perform Audit

Create CAPA Plan

Issue Report

Audit Questionnaire Questions Locked

Risk Assessment Check Plan Approvals

Follow-up

Responses received CAPA’s completed Observations closed Audit questionnaire locked

Vendor/Site responds

Close Audit

Audit Questionnaire Locked

SOP requires inspection of site at

regular intervals

Create Observation/

Findings

GenerateAudit Report

To Vendor/Site

VerifyCompletion

A Holistic Audit Management Solution

Preclinical GLP Auditing

Clinical GCP Auditing

EH&S AuditingGMP Auditing

Functional Auditing

Process Auditing

With the right level of executive sponsorship, you can leverage a system across the enterprise and

create a holistic audit management solution

Analysis and Reporting

DataManagement

Workflow Automation

Audit Trail &e-Signature

Business Rules Enforcement

Information Retrieval

Issue Identification

Issue Resolution


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Incidents

Audit

Management

Training

Management

Investigations

Risk Evaluation

Root Cause Analysis

Effectivity Analysis

Complaint

Handling

CAPA



Supplier Quality

Management

Enterprise Quality Management

Adverse Event Reporting

Product Registration Tracking

Why Implement a Global Audit Solution?

More Visibility:

Audit Actions CAPA QM

Audit Action Plans Change Control

Visibility Across all Functions

Automation:

Track all Audit Steps

Issue Resolution

Improve Cycle Times

Consistency:

Common Audit Elements w/ Flexibility

Audit Analytics

Audit Prioritization

Quality Systems in Three Dimensions

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Quality Process

GLP/GCP/GMP Supplier

Qualification Corporate

Standards EHS CAPA Change Control

Functional Area

Preclinical Clinical Internal

Manufacturing R&D Supplier

Management

Geography

Country Region Business Unit

EQMS and EDMS

People & Manual Process

EQMS / EDMS Interaction Points

Enterprise Quality Management System

Non-Conformances

Audit Management

Change Controls

Enterprise Document Management System

Complaints

Design History Files

Lot History Records

Design History Record

Standard Operating Procedures

Disconnected Processes Create

Lack of visibility

Data redundancy

Lengthened cycle times

Poor user experience

Degraded audit trail

Request Change

Impact Analysis

Plan

Execute

Implement

Author

Review

Approve

Train

Release

Change Control Document Control

The Document Challenge

Example Change Control Process

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Change Control Opened

Impact Analysis

Search for and link to impacted documents

Pre-Approval

Execute Change

Plan

Closed -Done

Post-Approval

Pending Implement

Pending Change

Plan

Action Item

Opened

PendingApproval

Work in Process

CompleteClosed -

Done

EffectiveV1.0

DraftV1.1

In Review

ReviewedIn

ApprovalApproved

V2.0

IssuedV2.0

EffectiveV.2.0

Train Release and Supersede

V1.0

Action Item is complete whendocument revision is complete

Create new draft version of impacted document

Action Item is closed when change is implemented


Document Management System


DataManagement

Workflow Automation

Audit Trail &e-Signature

Business Rules Enforcement

Information Retrieval

Issue Identification

Issue Resolution


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Text Goes Here

Text Goes Here

Text Goes Here


Incidents

Audit

Management

Training

Management

Investigations

Risk Evaluation

Root Cause Analysis

Effectivity Analysis

Complaint

Handling

CAPA



Supplier Quality

Management

Design or Spec Changes

EQMS and EDMS

SOP Updates for Read and Understand

Policy, Regulation, and SOP References

Risk Assessment Evidence

Objective Evidence

Quality Training Courses

Preventative Maintenance Plan

Design and Lot History Files

Adverse Event Reporting

Product Registration Tracking

New Regulations, New Expectations

EU 2011/62/EU Falsified Medicinal Products Directive

Update of regulation to address counterfeiting of drugs

Manufacturers of active substances and excipients are subject to inspection

Whether inside or outside of the EU, any manufacturer of ingredients intended for use in a drug product to be sold in the EU should follow GMP’s

Pharmaceutical manufacturers must have written confirmation that they have verified GMP compliance by suppliers

- Should be done through an audit of the supplier

- If a supplier is found to be non-compliant with GMP’s, pharmacompany is required to report this to local regulatory authority

- Suppliers are not allowed to self audit, or order third party audit as proof of compliance

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Update of regulation to address counterfeiting of drugs (cont.)

Manufacturers, importers & distributors must be registered with the competent authority in the country where they market products or provide active substances or excipients for products sold within the Union

Local findings of non-compliance are to be supplied by the exporting 3rd party country to the union

Importers, manufacturers & distributors of active substances who are established in the Union, must register with their authority- Must register at least 60 days prior to commencing activity

- Authority may require inspection prior to commencement

- Companies must report changes annually

- Any change that impacts quality or safety must be reported immediately

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Update of regulation to address counterfeiting of drugs (cont.)

Manufacturers, suppliers, importers & distributors “must maintain a quality system setting out responsibilities, processes and risk management measures in relation to their activities”

The competent authority of a Member State may carry out inspections of material manufacturers and suppliers at the specific request of the manufacturer

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Food & Drug Administration Safety & Innovation Act

Key highlights:

Signed into law July 9, 2012

Directs FDA to create a Unique Facility Identifier (UFI) system to electronically store registration & listing information

- Excipient manufacturers & importers required to have a UFI

- If a drug or device is from an unregistered facility it is misbranded

Increase in funding for inspections

Drug establishments will be inspected on a “risk-based” schedule

Foreign government inspections of foreign registered companies will be recognized

- FDA has taken enforcement action based on a non-FDA inspection

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Food & Drug Administration Safety & Innovation Act

Key highlights (cont.):

Allows FDA to request records & information prior to or in lieu of an inspection

Drugs will be misbranded if manufactured at any establishment that “delays, denies or limits an inspection or refuses to permit entry or inspection”

cGMP’s are to include “managing the risk and establishing the safety of raw materials, materials used in the manufacturing of drugs and finished drug products”

A new risk based standard of admission and screening for imported drug products to be implemented

Drug adulteration penalties of up to 20 years in prison and $1 million in fines established

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FDA Enforcement

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“However, there was no review and approval conducted by your QA group for this deviation report that was prepared by your third party supplier.”

“We reviewed your firm's written responses and conclude that they were not adequate to address these deviations because no evidence was provided to demonstrate that your firm will be able to adequately control the review and disposition process for nonconforming product. The proper review and disposition of nonconforming product is essential for ensuring the safety and effectiveness of devices”

“Complaint trending was not being performed, CAPA's were not opened based on complaints, and complaint trending is not part of the Management Review key performance indicators”

FDA Enforcement (continued)

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“We reviewed your firm's responses and conclude that they were not adequate because no evidence was provided to demonstrate that your firm will be able to investigate the cause of nonconformities relating to product, processes, and the quality system; verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device”

“Specifically, your firm has failed to implement a vendor management policy by not performing a audit of a vendor who provides your firm with a service for your product.”

Post Market

Operating Outside “The Four Walls”

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Supplier Quality Management

Supplier Audit

Supplier Qualification EOL

Text Goes Here

Lab Issues & Nonconformances

Deviations & Incidents

AuditManagement

Investigations

Risk Evaluation

Root Cause Analysis

ComplaintHandling

CAPA

Change ControlBatch / IT / Process / Document Material / Equipment

Supplier Nonconformance

Supplier Corrective Action

Supplier Change Control

Electronic Reporting

Registration Tracking

Change Management

Commitment Tracking

Recall Management

Creating the connected quality enterprise!

Effectiveness CheckEffectiveness Check

External Agencies

The Extended Quality Enterprise

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Mobile Employees

Mobile Devices

Suppliers, Contractors,CMOs,Distributors

Quality

R&D

Commercial Manufacturing

Regulatory Affairs

Preclinical/ Clinical

EHS

• Incidents

• Investigations

• Audits

• Commitments

• Product Complaints

• Supplier Defects

• Deviations

• Corrective Actions

• Change Control

• Trends

• Approvals

• Reports

• Status

• Audits

• NCs

• Commitments

• Audit Observations

• Corrective Actions

• Deviations / Events

• Product Complaints

• Certifications

Emerging Requirements & Capabilities

ExternalQuality Views

Regulatory Affairs

Thank You

The Technology of Quality

For more information, contact

Jay SmithDirector, Product ManagementSparta Systems [email protected]

Q&A

glp, gcp & gmp harmonization - veeva systems · we compare the regulations, explore ... • the...

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